活血通降方对Barrett食管模型大鼠食管化生的抑制作用及对PGRN和TNF-α/TNFR1/NF-κB/CDX2通路的影响  

Effect of Huoxue Tongjiang formula on esophageal metaplasia and its effect on PGRN and TNF-α/TNFR1/NF-κB/CDX2 pathway in rats with Barrett esophagus

作　　者：李培彩[1] 唐艳萍[1] 杨磊[1] 刘琰 刘思雨 LI Peicai;TANG Yanping;YANG Lei;LIU Yan;LIU Siyu(Department of GastroenterologyⅡ,Tianjin Nankai Hospital,Tianjin,300100,China)

机构地区：[1]天津市南开医院消化内科二,天津300100

出　　处：《中国中西医结合消化杂志》2025年第3期274-280,共7页Chinese Journal of Integrated Traditional and Western Medicine on Digestion

基　　金：国家自然科学基金资助项目(No:82204988,No:82074213,No:82274253)。

摘　　要：目的:研究活血通降方对Barrett食管(Barrett esophagus,BE)模型大鼠PGRN及TNF-α/TNFR1/NF-κB/CDX2通路的影响,探讨其防治食管BE化生的作用机制。方法:将SD大鼠随机分为对照组、模型组、西药组及中药高、中、低剂量组,每组10只。对照组行腹腔开关术,其余各组均采用“食管-十二指肠端侧吻合+保留全胃术联合铁剂注射”方法建立BE大鼠模型。造模4周后,各组分别给予相应剂量药物或相同体积生理盐水灌胃,2次/d,连续给药18周。苏木精-伊红染色评价食管黏膜病理表现;采用酶联免疫吸附法检测血清TNF-α、IL-8含量;采用蛋白免疫印记法检测食管组织中TNF-α、TNFR1、p-P65、CDX2、PGRN、GRN、MMP-12、SLPI和IL-8蛋白表达水平。结果:对照组大鼠未发生BE化生及肠化(intestinal metaplasia,IM),模型组大鼠BE化生率为83.3%,明显高于中药治疗各组的50.0%、37.5%、28.6%以及西药组的57.1%,差异有统计学意义(P=0.023)。模型组出现IM的比例为66.7%,明显高于中药治疗各组的33.3%、12.5%、14.3%以及西药组的42.9%,差异有统计学意义(P=0.044)。其中,中药中、高剂量组BE化生率及IM发生率均最低。与对照组相比,模型组大鼠血清中TNF-α、IL-8的含量,食管组织中TNF-α、TNFR1、p-P65、CDX2、GRN、MMP-12和IL-8的表达水平均明显升高(P<0.05),PGRN和SLPI的表达均显著下降(P<0.05)。给予药物干预后,中药各剂量组大鼠TNF-α、IL-8含量,食管组织中TNF-α、TNFR1、p-P65、CDX2、GRN、MMP-12和IL-8的表达水平均显著降低(P<0.05);PGRN和SLPI的表达均上调(P<0.05)。其中,中药中、高剂量组血清中TNF-α、IL-8的含量及食管组织中GRN表达的降低均优于西药组(P<0.05)。结论:活血通降方可有效预防和治疗BE的化生及IM的发生,其作用机制可能与上调PGRN的表达及抑制炎症因子TNF-α、IL-8等的释放,进而抑制TNF-α/TNFR1/NF-κB/CDX2信号通路的活化有关。Objective To explore the mechanism of the Huoxue Tongjiang formula in preventing and treating Barrett esophagus(BE)by investigating its effects on PGRN and the TNF-α/TNFR1/NF-κB/CDX2 pathway in rats with BE.Methods SD rats were randomly assigned to six groups:a control group,a model group,a Western medicine group,a high-dose traditional Chinese medicine group,a medium-dose traditional Chinese medicine group,and a low-dose traditional Chinese medicine group,with 10 rats in each group.The control group underwent laparotomy,whereas the other groups established BE rat models using the"esophago-duodenal end-to-side anastomosis combined with total gastrectomy and iron injection"method.Four weeks post-modeling,each group received the corresponding dose of medication or an equivalent volume of physiological saline via gavage,administered twice daily for a continuous duration of 18 weeks.HE staining was performed to evaluate the pathological changes in the esophageal mucosa.An enzyme-linked immunosorbent assay(ELISA)was utilized to detect serum levels of TNF-αand IL-8.Western blotting was employed to assess the expression levels of TNF-α,TNFR1,p-P65,CDX2,PGRN,GRN,MMP-12,SLPI,and IL-8 proteins in the esophageal tissues.Results No BE metaplasia or intestinal metaplasia(IM)was observed in the control group.In contrast,the BE metaplasia rate in the model group was 83.3%,significantly higher than the rates of 50.0%,37.5%,and 28.6%in the traditional Chinese medicine treatment groups,as well as 57.1%in the Western medicine group(P=0.023).The incidence of IM in the model group was 66.7%,significantly higher than the incidences of 33.3%,12.5%,and 14.3%in the traditional Chinese medicine treatment groups and 42.9%in the Western medicine group(P=0.044).Among these groups,the BE metaplasia rate and IM incidence were lowest in the medium and high-dose traditional Chinese medicine groups.Compared to the control group,serum levels of TNF-αand IL-8 in the model group,along with expression levels of TNF-α,TNFR1,p-P65,CDX2,GRN,MMP-12

关 键 词：反流性食管炎 活血通降方 肠上皮化生 CDX2 颗粒蛋白原 

分 类 号：R256.3[医药卫生—中医内科学]